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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection

Published on: November 7, 2018

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Functional cure of hepatitis B requires silencing covalently closed circular and integrated hepatitis B virus DNA

Marc G Ghany1, Anna S Lok2

  • 1Liver Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA.

The Journal of Clinical Investigation
|September 15, 2022
PubMed

Insights

A new PCR assay can now differentiate hepatitis B surface antigen (HBsAg) sources. This tool helps understand integrated HBV DNA

Area of Science:

  • Hepatology
  • Virology
  • Molecular Biology

Background:

  • Chronic hepatitis B virus (HBV) infection is a significant global health concern.
  • Hepatitis B surface antigen (HBsAg) loss signifies a functional cure for HBV.
  • Covalently closed circular DNA (cccDNA) and integrated HBV DNA (iDNA) are key sources of HBsAg, with cccDNA predominant in HBeAg-positive and iDNA in HBeAg-negative patients.

Purpose of the Study:

  • To develop a method distinguishing HBsAg sources (cccDNA vs. iDNA).
  • To assess the contribution of different HBsAg sources in patients receiving nucleos(t)ide analog antivirals.
  • To provide a tool for evaluating novel therapies aimed at a functional HBV cure.

Main Methods:

  • Development of a polymerase chain reaction (PCR)-based assay.
  • Differentiation of HBsAg originating from cccDNA versus iDNA.
  • Analysis of HBsAg sources in patients undergoing antiviral therapy.

Main Results:

  • A novel PCR assay successfully differentiated HBsAg sources.
  • The study explored the relative contributions of cccDNA and iDNA to HBsAg production.
  • Findings provide insights into HBsAg origins in patients on nucleos(t)ide analogs.

Conclusions:

  • A new assay enables distinction between cccDNA and iDNA as HBsAg sources.
  • Understanding iDNA's role is crucial for achieving a functional HBV cure.
  • This tool can guide the development of targeted therapies for HBV functional cure.

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